The Expression of Dual Oxidase, Thyroid Peroxidase, and Caveolin-1 Differs According to the Type of Immune Response (TH1/TH2) Involved in Thyroid Autoimmune Disorders

Context: Hashimoto's thyroiditis (HT) and Graves' disease (GD) are thyroid autoimmune disorders driven by Th1 and Th2 immune responses, respectively. Caveolin-1 (Cav-1), thyroid peroxidase (TPO), and dual oxidase (DUOX) are thought to be part of the thyroxisome, which is essential to maintain thyroid hormone synthesis, at the apical membrane. Objectives: To analyze the thyroxisome in HT and GD thyroids, we investigated Cav-1, DUOX, and TPO expression as well as markers of oxidative stress (OS), cell proliferation, apoptosis, and antioxidant defenses. The effects of cytokines on Cav-1 expression were analyzed in vitro. Results: In HT, the decrease in Cav-1, DUOX, and TPO expression was marked in follicles having the morphological aspect of active follicles in normal glands and thus called active-like follicles. T4 was not detected in the colloid but in the cytoplasm as well as DUOX and TPO. These abnormalities were associated with increased OS and cell damage. In the hypofunctioning follicles of HT and normal thyroids, Cav-1, DUOX, and TPO were not expressed. In GD, they were expressed at the apical pole of thyrocytes, and T4 accumulated in the colloid of all follicles. Th1 cytokines IL-1α/interferonγ decreased Cav-1 expression in vitro, whereas the Th2 cytokine IL-4 had no effect. Conclusion: Th1 cytokine-induced down-regulation of Cav-1 could be responsible for intracytoplasmic T4 synthesis and mislocalization of DUOX and TPO, suggesting an important role for Cav-1 in the preservation of thyroxisome integrity. The thyroxisome's disruption, leading to uncontrolled OS and cell apoptosis, is a key, event in HT pathogenesis.